The scanty epidemiologic evidence available suggests that enterotoxigenic Escherichia coli (ETEC) are usually spread by contaminated food and water vehicles; little is known of the risk of secondary spread by contact transmission. Studies carried out in a 22-bed isolation Ward at the U. of Maryland Hospital gave the opportunity to determine whether individuals excreting ETEC, with and without diarrhea, would transmit the pathogen to controls living in close contact. In one combined study, seven volunteers who had ingested 10(8) virulent ETEC (strain H10407), were housed day and night for two weeks with eight other volunterrs participating in an intranasal attenuated influenza vaccine study. In a second study, four persons ingesting 10(8) ETEC (strain 214-4) lived with 13 who were inoculated with intranasal influenza vaccine. The individuals in the E. coli and influenza groups were randomly mixed in bedrooms and shared bathrooms, dining and recreation areas of the ward. Seven persons who ingested ETEC developed diarrhea; all 11 excreted the pathogen (10(7)-10(9) organisms/gm or ml of stool), and 10 had significant rises in anti-O or antitoxin antibody. In contrast, no influenza vaccinees, despite close sharing of facilities, developed diarrhea, excreted ETEC or had rises in antibody to E. coli antigens. These data suggest that ETEC are not readily transmitted to healthy adults by direct person-to-person contact. Precautions to prevent contamination of shared food sources would appear to be the most rational intervention to avoid secondary cases of ETEC diarrhea.